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. 2024 Apr 22;25(8):4557.
doi: 10.3390/ijms25084557.

Syndecans, Exostosins and Sulfotransferases as Potential Synovial Inflammation Moderators in Patients with Hip Osteoarthritis

Matko Rošin  1 , Nela Kelam  2 , Ivana Jurić  3 , Anita Racetin  2 , Marin Ogorevc  2 , Brieuc Corre  4 , Davor Čarić  1 , Natalija Filipović  2 , Katarina Vukojević  2   5
Affiliations

Syndecans, Exostosins and Sulfotransferases as Potential Synovial Inflammation Moderators in Patients with Hip Osteoarthritis

Matko Rošin et al. Int J Mol Sci. .

Abstract

The gradual deterioration of articular cartilage was thought to be the central event in osteoarthritis (OA), but recent studies demonstrated the importance of low-grade synovitis in the progression of OA. The Syndecan (SDC) family of membrane proteoglycans is known to be involved in the regulation of inflammation, but there is limited evidence considering the role of syndecans in OA synovitis. Our study aimed to investigate the hip OA synovial membrane expression patterns of SDC1, SDC2 and SDC4, as well as exostosins and sulfotransferases (enzymes involved in the polymerisation and modification of syndecans' heparan sulphate chains). Synovial membrane samples of patients with OA (24) were divided into two groups according to their Krenn synovitis score severity. The immunohistochemical expressions of SDC1, SDC2, SDC4, EXT1, EXT2, NDST1 and NDST2 in synovial intima and subintima were then analysed and compared with the control group (patients with femoral neck fracture). According to our study, the immunoexpression of SDC1, NDST1 and EXT2 is significantly increased in the intimal cells of OA synovial membrane in patients with lower histological synovitis scores and SDC4 in patients with higher synovitis scores, in comparison with non-OA controls. The difference in the expression of SDC2 among the OA and non-OA groups was insignificant. SDC1, SDC4, NDST1 and EXT2 seem to be involved as inflammation moderators in low-grade OA synovitis and, therefore, should be further investigated as potential markers of disease progression and therapeutic goals.

Keywords: exostosin; osteoarthritis; sulfotransferase; syndecan; synovial membrane.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Immunoexpression of SDC1 (syndecan-1) in the synovial membrane of patients with hip osteoarthritis (OA). (A) Hip synovium of patients without OA (controls), (B) hip synovium of patients with low synovitis score (Krenn score 0–2), (C) hip synovium of patients with higher synovitis score of OA (Krenn score ≥ 3); int—intima, sub—subintima, bv—blood vessel. SDC1-positive cells (red signal) can be seen in the intima (arrows) and subintima (arrowheads) of all analysed groups (A–C). 4′,6-diamidino-2-phenylindole (DAPI) stains all cell nuclei blue. SDC1 merged with DAPI nuclear staining is displayed in the far right column (merge). Images were taken at a magnification of ×40. The scale bar is 100 μm and refers to all images.
Figure 2
Figure 2
Statistical analyses of protein immunoexpression in the synovial membrane of patients with hip osteoarthritis (OA). INT—intima, SUB—subintima, CTRL—controls, LSS—low synovitis score of OA (Krenn score 0–2), HSS—higher synovitis score of OA (Krenn score ≥ 3). All analyses were performed using two-way ANOVA with Tukey’s post hoc test. The bars of the graphs represent the mean area percentage of the immunofluorescence signal of the analysed proteins, while the error bars represent the standard deviation. Asterisks mark significant differences: * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.
Figure 3
Figure 3
Immunoexpression of SDC2 (syndecan-2) in the synovial membrane of patients with hip osteoarthritis (OA). (A) Hip synovium of patients without OA (controls), (B) hip synovium of patients with low synovitis score (Krenn score 0–2), (C) hip synovium of patients with higher synovitis score of OA (Krenn score ≥ 3); int—intima, sub—subintima, bv—blood vessel. SDC2-positive cells (green signal) can be seen in the intima (arrows) and subintima (arrowheads) of all analysed groups (A–C). SDC2 positivity can be seen in some cells of subintimal blood vessels (A–C). 4′,6-diamidino-2-phenylindole (DAPI) stains all cell nuclei blue. SDC2 merged with DAPI nuclear staining is displayed in the far right column (merge). Images were taken at a magnification of ×40. The scale bar is 100 μm and refers to all images.
Figure 4
Figure 4
Immunoexpression of SDC4 (syndecan-4) in the synovial membrane of patients with hip osteoarthritis (OA). (A) Hip synovium of patients without OA (controls), (B) Hip synovium of patients with low synovitis score of OA (Krenn score 0–2), (C) hip synovium of patients with higher synovitis score of OA (Krenn score ≥ 3); int—intima, sub—subintima, bv—blood vessel. SDC4-positive cells (green signal) can be seen in the intima (arrows) and subintima (arrowheads) of all analysed groups (A–C). 4′,6-diamidino-2-phenylindole (DAPI) stains all cell nuclei blue. SDC4 merged with DAPI nuclear staining is displayed in the far right column (merge). Images were taken at a magnification of ×40. The scale bar is 100 μm and refers to all images.
Figure 5
Figure 5
Immunoexpression of NDST1 (N-deacetylase/N-sulfotransferase 1) in the synovial membrane of patients with hip osteoarthritis (OA). (A) Hip synovium of patients without OA (controls), (B) hip synovium of patients with low synovitis score of OA (Krenn score 0–2), (C) hip synovium of patients with higher synovitis score of OA (Krenn score ≥ 3); int—intima, sub—subintima, bv—blood vessel. NDST1-positive cells (green signal) can be seen in the intima (arrows) and subintima (arrowheads) of all analysed groups (A–C). Strong positivity can be observed in the subintimal blood vessels of the mild OA group (B). 4′,6-diamidino-2-phenylindole (DAPI) stains all cell nuclei blue. NDST1 merged with DAPI nuclear staining is displayed in the far right column (merge). Images were taken at a magnification of ×40. The scale bar is 100 μm and refers to all images.
Figure 6
Figure 6
Immunoexpression of NDST2 (N-deacetylase/N-sulfotransferase 2) in the synovial membrane of patients with hip osteoarthritis (OA). (A) Hip synovium of patients without OA (controls), (B) hip synovium of patients with low synovitis score of OA (Krenn score 0–2), (C) hip synovium of patients with higher synovitis score of OA (Krenn score ≥ 3); int—intima, sub—subintima, bv—blood vessel. NDST2-positive cells (green signal) can be seen in the intima (arrows) and subintima (arrowheads) of all analysed groups (A–C). 4′,6-diamidino-2-phenylindole (DAPI) stains all cell nuclei blue. NDST2 merged with DAPI nuclear staining is displayed in the far right column (merge). Images were taken at a magnification of ×40. The scale bar is 100 μm and refers to all images.
Figure 7
Figure 7
Immunoexpression of EXT1 (exostosin 1) in the synovial membrane of patients with hip osteoarthritis (OA). (A) Hip synovium of patients without OA (controls), (B) hip synovium of patients with low synovitis score of OA (Krenn score 0–2), (C) hip synovium of patients with higher synovitis score of OA (Krenn score ≥ 3); int—intima, sub—subintima, bv—blood vessel. EXT1-positive cells (green signal) can be seen in the intima (arrows) and subintima (arrowheads) of all analysed groups (A–C). Endothelial cells of subintimal blood vessels demonstrate strong EXT1 positivity, especially in OA patients (B,C). 4′,6-diamidino-2-phenylindole (DAPI) stains all cell nuclei blue. EXT1 merged with DAPI nuclear staining is displayed in the far right column (merge). Images were taken at a magnification of ×40. The scale bar is 100 μm and refers to all images.
Figure 8
Figure 8
Immunoexpression of EXT2 (exostosin 2) in the synovial membrane of patients with hip osteoarthritis (OA). (A) Hip synovium of patients without OA (controls), (B) hip synovium of patients with low synovitis score of OA (Krenn score 0–2), (C) hip synovium of patients with higher synovitis score of OA (Krenn score ≥ 3); int—intima, sub—subintima, bv—blood vessel. EXT2-positive cells (green signal) can be seen in the intima (arrows) and subintima (arrowheads) of all analysed groups (A–C). Strong positivity can be observed in the subintimal blood vessels of the mild-OA group (B). 4′,6-diamidino-2-phenylindole (DAPI) stains all cell nuclei blue. EXT2 merged with DAPI nuclear staining is displayed in the far right column (merge). Images were taken at a magnification of ×40. The scale bar is 100 μm and refers to all images.
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References

    1. Litwic A., Edwards M.H., Dennison E.M., Cooper C. Epidemiology and Burden of Osteoarthritis. Br. Med. Bull. 2013;105:185–199. doi: 10.1093/bmb/lds038. - DOI - PMC - PubMed
    1. Courties A., Berenbaum F. Is hip osteoarthritis preventable? Jt. Bone Spine. 2020;87:371–375. doi: 10.1016/j.jbspin.2019.11.010. - DOI - PubMed
    1. Salmon J.H., Rat A.C., Achit H., Ngueyon-Sime W., Gard C., Guillemin F., Jolly D., Fautrel B. Health resource use and costs of symptomatic knee and/or hip osteoarthritis. Osteoarthr. Cartil. 2019;27:1011–1017. doi: 10.1016/j.joca.2019.03.005. - DOI - PubMed
    1. Vina E.R., Kwoh C.K. Epidemiology of osteoarthritis: Literature update. Curr. Opin. Rheumatol. 2018;30:160–167. doi: 10.1097/BOR.0000000000000479. - DOI - PMC - PubMed
    1. GBD 2021 Osteoarthritis Collaborators Global, regional, and national burden of osteoarthritis, 1990–2020 and projections to 2050: A systematic analysis for the Global Burden of Disease Study 2021. Lancet Rheumatol. 2023;21:e508–e522. - PMC - PubMed

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